JPH0696542B2 - 眼用保存製剤およびその製法 - Google Patents
眼用保存製剤およびその製法Info
- Publication number
- JPH0696542B2 JPH0696542B2 JP63227343A JP22734388A JPH0696542B2 JP H0696542 B2 JPH0696542 B2 JP H0696542B2 JP 63227343 A JP63227343 A JP 63227343A JP 22734388 A JP22734388 A JP 22734388A JP H0696542 B2 JPH0696542 B2 JP H0696542B2
- Authority
- JP
- Japan
- Prior art keywords
- volume
- weight
- ophthalmic
- nsaid
- amount
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
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- 238000009472 formulation Methods 0.000 title claims abstract description 59
- 239000003755 preservative agent Substances 0.000 title claims abstract description 47
- 230000002335 preservative effect Effects 0.000 title claims abstract description 43
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims abstract description 79
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims abstract description 78
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 14
- 125000001453 quaternary ammonium group Chemical group 0.000 claims abstract description 14
- 239000008135 aqueous vehicle Substances 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 28
- 229920004914 octoxynol-40 Polymers 0.000 claims description 26
- 239000004094 surface-active agent Substances 0.000 claims description 25
- 239000007864 aqueous solution Substances 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 21
- 239000008213 purified water Substances 0.000 claims description 19
- 239000011780 sodium chloride Substances 0.000 claims description 16
- 229960004384 ketorolac tromethamine Drugs 0.000 claims description 15
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 claims description 15
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 14
- 239000002738 chelating agent Substances 0.000 claims description 12
- 239000012530 fluid Substances 0.000 claims description 12
- 230000000087 stabilizing effect Effects 0.000 claims description 9
- 239000007951 isotonicity adjuster Substances 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 abstract description 14
- 239000002736 nonionic surfactant Substances 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 10
- 238000001356 surgical procedure Methods 0.000 abstract description 10
- 206010010741 Conjunctivitis Diseases 0.000 abstract description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 abstract description 4
- 208000020564 Eye injury Diseases 0.000 abstract description 4
- 208000010412 Glaucoma Diseases 0.000 abstract description 4
- 206010046851 Uveitis Diseases 0.000 abstract description 4
- 208000014674 injury Diseases 0.000 abstract description 4
- 230000008733 trauma Effects 0.000 abstract description 4
- 206010058202 Cystoid macular oedema Diseases 0.000 abstract 1
- 208000001344 Macular Edema Diseases 0.000 abstract 1
- 201000010206 cystoid macular edema Diseases 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 35
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 22
- 210000001508 eye Anatomy 0.000 description 21
- 229960004752 ketorolac Drugs 0.000 description 21
- 229960000686 benzalkonium chloride Drugs 0.000 description 20
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 19
- 238000011282 treatment Methods 0.000 description 19
- 239000004615 ingredient Substances 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 14
- 208000030533 eye disease Diseases 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 239000000546 pharmaceutical excipient Substances 0.000 description 13
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 12
- 239000002997 ophthalmic solution Substances 0.000 description 11
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- 206010061218 Inflammation Diseases 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 229940054534 ophthalmic solution Drugs 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229960000905 indomethacin Drugs 0.000 description 6
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 6
- 230000004888 barrier function Effects 0.000 description 5
- 229960001259 diclofenac Drugs 0.000 description 5
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 5
- 229960002390 flurbiprofen Drugs 0.000 description 5
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 5
- -1 BAC Chemical class 0.000 description 4
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 208000002205 allergic conjunctivitis Diseases 0.000 description 4
- 210000002159 anterior chamber Anatomy 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 4
- 208000024998 atopic conjunctivitis Diseases 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 238000005375 photometry Methods 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 238000004321 preservation Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 3
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 3
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 208000003251 Pruritus Diseases 0.000 description 3
- 125000000129 anionic group Chemical group 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 3
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229960003898 flurbiprofen sodium Drugs 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- GNMBMOULKUXEQF-UHFFFAOYSA-M sodium;2-(3-fluoro-4-phenylphenyl)propanoate;dihydrate Chemical compound O.O.[Na+].FC1=CC(C(C([O-])=O)C)=CC=C1C1=CC=CC=C1 GNMBMOULKUXEQF-UHFFFAOYSA-M 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010015946 Eye irritation Diseases 0.000 description 2
- 206010015993 Eyelid oedema Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000003732 agents acting on the eye Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- OIPMQULDKWSNGX-UHFFFAOYSA-N bis[[ethoxy(oxo)phosphaniumyl]oxy]alumanyloxy-ethoxy-oxophosphanium Chemical compound [Al+3].CCO[P+]([O-])=O.CCO[P+]([O-])=O.CCO[P+]([O-])=O OIPMQULDKWSNGX-UHFFFAOYSA-N 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 230000002327 eosinophilic effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 231100000013 eye irritation Toxicity 0.000 description 2
- 210000000744 eyelid Anatomy 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 201000004614 iritis Diseases 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229940125702 ophthalmic agent Drugs 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
- 229940033663 thimerosal Drugs 0.000 description 2
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical compound CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 1
- BPZYKPINOMFZGY-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)c1ccc(OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO)cc1 BPZYKPINOMFZGY-UHFFFAOYSA-N 0.000 description 1
- AFYLOVCVJUMURG-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)c1ccc(OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO)cc1 AFYLOVCVJUMURG-UHFFFAOYSA-N 0.000 description 1
- HNLXNOZHXNSSPN-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCOCCOCCOCCO)C=C1 HNLXNOZHXNSSPN-UHFFFAOYSA-N 0.000 description 1
- BDOYKFSQFYNPKF-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;sodium Chemical compound [Na].[Na].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O BDOYKFSQFYNPKF-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 206010011033 Corneal oedema Diseases 0.000 description 1
- 206010014080 Ecchymosis Diseases 0.000 description 1
- 206010015943 Eye inflammation Diseases 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 206010022941 Iridocyclitis Diseases 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 206010030111 Oedema mucosal Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- YYVFXSYQSOZCOQ-UHFFFAOYSA-N Oxyquinoline sulfate Chemical compound [O-]S([O-])(=O)=O.C1=C[NH+]=C2C(O)=CC=CC2=C1.C1=C[NH+]=C2C(O)=CC=CC2=C1 YYVFXSYQSOZCOQ-UHFFFAOYSA-N 0.000 description 1
- 206010036346 Posterior capsule opacification Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 201000004612 anterior uveitis Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
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- 210000005252 bulbus oculi Anatomy 0.000 description 1
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- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229920003090 carboxymethyl hydroxyethyl cellulose Polymers 0.000 description 1
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- 229920002678 cellulose Polymers 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
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- 201000004778 corneal edema Diseases 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 210000002555 descemet membrane Anatomy 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
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- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
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- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000005722 itchiness Effects 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-M ketorolac(1-) Chemical compound [O-]C(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 150000002731 mercury compounds Chemical class 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 229940066429 octoxynol Drugs 0.000 description 1
- 229920004907 octoxynol-12 Polymers 0.000 description 1
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- 229920002114 octoxynol-9 Polymers 0.000 description 1
- 229940098514 octoxynol-9 Drugs 0.000 description 1
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- 229940023490 ophthalmic product Drugs 0.000 description 1
- 229940100654 ophthalmic suspension Drugs 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- RQGPLDBZHMVWCH-UHFFFAOYSA-N pyrrolo[3,2-b]pyrrole Chemical class C1=NC2=CC=NC2=C1 RQGPLDBZHMVWCH-UHFFFAOYSA-N 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Detergent Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9617387A | 1987-09-11 | 1987-09-11 | |
US96,173 | 1987-09-11 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH01104023A JPH01104023A (ja) | 1989-04-21 |
JPH0696542B2 true JPH0696542B2 (ja) | 1994-11-30 |
Family
ID=22256043
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP63227343A Expired - Lifetime JPH0696542B2 (ja) | 1987-09-11 | 1988-09-09 | 眼用保存製剤およびその製法 |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP0306984B1 (fi) |
JP (1) | JPH0696542B2 (fi) |
KR (1) | KR950013754B1 (fi) |
AT (1) | ATE74750T1 (fi) |
AU (1) | AU626798B2 (fi) |
CA (1) | CA1328614C (fi) |
DE (1) | DE3870111D1 (fi) |
DK (1) | DK174702B1 (fi) |
FI (1) | FI94924C (fi) |
HK (1) | HK27894A (fi) |
HU (2) | HU199072B (fi) |
IE (1) | IE60717B1 (fi) |
IL (1) | IL87724A (fi) |
NO (1) | NO175404C (fi) |
NZ (1) | NZ226100A (fi) |
PH (1) | PH25422A (fi) |
ZA (1) | ZA886757B (fi) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5414011A (en) * | 1987-09-11 | 1995-05-09 | Syntex (U.S.A.) Inc. | Preservative system for ophthalmic formulations |
ATE103182T1 (de) * | 1989-09-21 | 1994-04-15 | Ciba Vision Ag | Antimikrobielle zusammensetzungen. |
IL95942A0 (en) * | 1989-10-13 | 1991-07-18 | Syntex Inc | Collagen-containing ophthalmic formulation |
US5464609A (en) * | 1990-03-16 | 1995-11-07 | The Procter & Gamble Company | Use of ketorolac for treatment of oral diseases and conditions |
AU661818B2 (en) * | 1990-03-16 | 1995-08-10 | Procter & Gamble Company, The | Use of ketorolac for treatment of periodontal disease |
AU653768B2 (en) * | 1990-12-27 | 1994-10-13 | Advanced Medical Optics, Inc. | Method and composition for disinfecting contact lenses |
US5093105A (en) * | 1991-04-09 | 1992-03-03 | Merck Frosst Canada, Inc. | Radiopharmaceutical bacteriostats |
US5227152A (en) * | 1991-04-09 | 1993-07-13 | Merck Frosst Canada, Inc. | Radiopharmaceutical bacteriostats |
US5306482A (en) * | 1991-04-09 | 1994-04-26 | Merck Frosst Canada, Inc. | Radiopharmaceutical bacteriostats |
WO1995016435A2 (en) * | 1993-12-17 | 1995-06-22 | Alcon Laboratories, Inc. | Improved intraocular irrigating solution containing non-steroidal antiinflammatory agent |
US5474985A (en) * | 1993-12-22 | 1995-12-12 | The Regents Of The University Of California | Preventing and treating elevated intraocular pressure associated with administered or endogenous steroids using non-steroidal cyclooxygenase inhibitors |
ES2079320B1 (es) * | 1994-05-17 | 1996-10-16 | Cusi Lab | Disolucion oftalmica a base de un diclofenaco y tobramicina y sus aplicaciones. |
WO1995033456A2 (en) * | 1994-06-07 | 1995-12-14 | Telor Ophthalmic Pharmaceuticals, Inc. | Reducing intraocular pressure using aryloxy- and aryl-acetic acids |
CA2201134A1 (en) * | 1994-10-10 | 1996-04-18 | Alfred Sallmann | Ophthalmic and aural compositions containing diclofenac potassium |
US5603929A (en) * | 1994-11-16 | 1997-02-18 | Alcon Laboratories, Inc. | Preserved ophthalmic drug compositions containing polymeric quaternary ammonium compounds |
RU2136252C1 (ru) * | 1995-01-20 | 1999-09-10 | Вакамото Фармасьютикал Ко., Лтд. | Противовоспалительные глазные капли |
US5599535A (en) * | 1995-06-07 | 1997-02-04 | Regents Of The University Of California | Methods for the cyto-protection of the trabecular meshwork |
US5674888A (en) * | 1995-06-07 | 1997-10-07 | University Of California | Method for the treatment of a trabecular meshwork whose cells are subject to inhibition of cell division |
TW434023B (en) * | 1995-09-18 | 2001-05-16 | Novartis Ag | Preserved ophthalmic composition |
JPH09278653A (ja) * | 1996-04-05 | 1997-10-28 | Santen Pharmaceut Co Ltd | 網膜疾患治療剤 |
MX9701946A (es) * | 1997-03-14 | 1998-04-30 | Arturo Jimenez Bayardo | Solucion oftalmica transportadora. |
DE19729879C2 (de) | 1997-07-11 | 1999-07-08 | Mann Gerhard Chem Pharm Fab | Lagerstabile ophthalmische Zusammensetzungen, umfassend Diclofenac und Ofloxacin |
JP2006111636A (ja) * | 1997-12-26 | 2006-04-27 | Astellas Pharma Inc | 徐放性医薬組成物 |
DE60039043D1 (de) * | 1999-03-02 | 2008-07-10 | Vitreo Retinal Technologies In | Mittel für intravitreale verabreichung zur behandlung oder vorbeugung von augenerkrankungen |
DE19918324A1 (de) * | 1999-04-22 | 2000-10-26 | Mann Gerhard Chem Pharm Fab | Pharmazeutische Zusammensetzung wirksam gegen durch Bakterien, Viren, Pilze, Hefen und Protozoen verursachte Krankheitszustände |
US20020035107A1 (en) | 2000-06-20 | 2002-03-21 | Stefan Henke | Highly concentrated stable meloxicam solutions |
DE10161077A1 (de) | 2001-12-12 | 2003-06-18 | Boehringer Ingelheim Vetmed | Hochkonzentrierte stabile Meloxicamlösungen zur nadellosen Injektion |
US8992980B2 (en) | 2002-10-25 | 2015-03-31 | Boehringer Ingelheim Vetmedica Gmbh | Water-soluble meloxicam granules |
PT1586316E (pt) | 2003-01-21 | 2008-05-28 | Senju Pharma Co | Preparação líquida aquosa contendo ácido 2-amino-3-(4- bromobenzoil)fenilacético |
US8008338B2 (en) | 2003-06-03 | 2011-08-30 | Allergan, Inc. | Ketorolac tromethamine compositions for treating or preventing ocular pain |
PL1654002T5 (pl) | 2003-08-07 | 2014-06-30 | Allergan Inc | Kompozycje do dostarczania środków terapeutycznych do oczu |
EP1568369A1 (en) | 2004-02-23 | 2005-08-31 | Boehringer Ingelheim Vetmedica Gmbh | Use of meloxicam for the treatment of respiratory diseases in pigs |
US20050261243A1 (en) * | 2004-04-21 | 2005-11-24 | Peyman Gholam A | Antiprostaglandins for the treatment of ocular pathologies |
US9161905B2 (en) * | 2005-01-12 | 2015-10-20 | Ocular Research Of Boston, Inc. | Dry eye treatment |
US9192571B2 (en) | 2008-03-03 | 2015-11-24 | Allergan, Inc. | Ketorolac tromethamine compositions for treating or preventing ocular pain |
US9101529B2 (en) | 2009-10-12 | 2015-08-11 | Boehringer Ingelheim Vetmedica Gmbh | Containers for compositions comprising meloxicam |
BR112012022073A2 (pt) | 2010-03-03 | 2017-10-31 | Boehringer Ingelheim Vetmedica Gmbh | uso de meloxicam para o tratamento de longa duração de distúrbios musculoesqueletais em gatos. |
US9795568B2 (en) | 2010-05-05 | 2017-10-24 | Boehringer Ingelheim Vetmedica Gmbh | Low concentration meloxicam tablets |
JP2013082682A (ja) * | 2011-09-29 | 2013-05-09 | Senju Pharmaceut Co Ltd | 亜塩素酸塩を含有する水性製剤 |
CN110448530A (zh) * | 2018-05-07 | 2019-11-15 | 北京蓝丹医药科技有限公司 | 一种氟比洛芬酯注射液 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4087538A (en) * | 1976-09-09 | 1978-05-02 | Merck & Co., Inc. | Ophthalmic suspensions |
DE3026402A1 (de) * | 1980-07-11 | 1982-02-04 | Syntex Corp., Palo Alto, Calif. | Die verwendung analgetischer und nicht-hormonaler, entzuendungshemmender mittel bei der behandlung von mikrovaskulaeren erkrankungen |
HU195918B (en) * | 1984-03-14 | 1988-08-29 | Jerome Corbiere | Process for producing pharmaceutical compositions containing non-steroide antiflogistic active components |
-
1988
- 1988-09-09 HU HU884648A patent/HU199072B/hu unknown
- 1988-09-09 DK DK198805056A patent/DK174702B1/da not_active IP Right Cessation
- 1988-09-09 JP JP63227343A patent/JPH0696542B2/ja not_active Expired - Lifetime
- 1988-09-09 KR KR1019880011664A patent/KR950013754B1/ko not_active Expired - Lifetime
- 1988-09-09 AU AU22042/88A patent/AU626798B2/en not_active Expired
- 1988-09-09 ZA ZA886757A patent/ZA886757B/xx unknown
- 1988-09-09 FI FI884160A patent/FI94924C/fi not_active IP Right Cessation
- 1988-09-09 IL IL87724A patent/IL87724A/xx not_active IP Right Cessation
- 1988-09-09 NZ NZ226100A patent/NZ226100A/en unknown
- 1988-09-09 DE DE8888114804T patent/DE3870111D1/de not_active Expired - Lifetime
- 1988-09-09 PH PH37525A patent/PH25422A/en unknown
- 1988-09-09 AT AT88114804T patent/ATE74750T1/de not_active IP Right Cessation
- 1988-09-09 IE IE274088A patent/IE60717B1/en not_active IP Right Cessation
- 1988-09-09 EP EP88114804A patent/EP0306984B1/en not_active Expired - Lifetime
- 1988-09-09 CA CA000576880A patent/CA1328614C/en not_active Expired - Lifetime
- 1988-09-09 NO NO884020A patent/NO175404C/no not_active IP Right Cessation
-
1994
- 1994-03-24 HK HK278/94A patent/HK27894A/en not_active IP Right Cessation
- 1994-07-01 HU HU94P/P00006P patent/HU210610A9/hu unknown
Also Published As
Publication number | Publication date |
---|---|
EP0306984B1 (en) | 1992-04-15 |
DK505688D0 (da) | 1988-09-09 |
AU626798B2 (en) | 1992-08-13 |
ATE74750T1 (de) | 1992-05-15 |
FI884160L (fi) | 1989-03-12 |
HU210610A9 (en) | 1995-05-29 |
ZA886757B (en) | 1990-05-30 |
HK27894A (en) | 1994-03-31 |
JPH01104023A (ja) | 1989-04-21 |
EP0306984A1 (en) | 1989-03-15 |
IL87724A0 (en) | 1989-02-28 |
NO175404C (no) | 1994-10-12 |
AU2204288A (en) | 1989-03-16 |
NO175404B (no) | 1994-07-04 |
PH25422A (en) | 1991-07-01 |
NO884020L (no) | 1989-03-13 |
IL87724A (en) | 1992-01-15 |
IE882740L (en) | 1989-03-11 |
CA1328614C (en) | 1994-04-19 |
NZ226100A (en) | 1990-12-21 |
NO884020D0 (no) | 1988-09-09 |
FI94924C (fi) | 1995-11-27 |
KR950013754B1 (ko) | 1995-11-15 |
HU199072B (en) | 1990-01-29 |
HUT47839A (en) | 1989-04-28 |
DK505688A (da) | 1989-03-12 |
FI884160A0 (fi) | 1988-09-09 |
IE60717B1 (en) | 1994-08-10 |
DK174702B1 (da) | 2003-09-29 |
DE3870111D1 (de) | 1992-05-21 |
FI94924B (fi) | 1995-08-15 |
KR890004691A (ko) | 1989-05-09 |
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